Case report: novel DNAH11 compound heterozygous variants including an exon 30-54 duplication in a child with a highly suggestive primary ciliary dyskinesia phenotype.

Primary ciliary dyskinesia (PCD) is a rare disorder characterized by dysfunction of motile cilia and chronic progressive respiratory disease, mianly inherited in an autosomal recessive manner. Biallelic variants in dynein axonemal heavy chain 11 (DNAH11) have been reported in association with PCD and are typically associated with normal ciliary ultrastructure. In addition, exon-level copy number variants (CNVs) in DNAH11, particularly duplications, remain poorly characterized and are prone to being overlooked by conventional sequencing workflows. We report a 9-year-old Chinese girl with recurrent lower respiratory tract infections, chronic pansinusitis, and bronchiectasis. Pulmonary function testing showed isolated small-airway dysfunction with preserved FEV1, with nasal nitric oxide (nNO) severely reduced (5.4 nL/min). Trio whole-exome sequencing integrated with read-depth CNV analysis detected novel compound heterozygous DNAH11 variants: a paternal inherited missense variant (c.6556A>C, p.Thr2186Pro) and a previously unreported maternally derived intragenic duplication encompassing exons 30-54. The missense variant was confirmed by Sanger sequencing, and the exon-level dosage gain was confirmed by qPCR. This case expands the spectrum of DNAH11 variants and highlights the importance of incorporating CNV detection into exome-based diagnostic process for children with a highly suggestive PCD phenotype.